Open Access Research article

Shared functions of plant and mammalian StAR-related lipid transfer (START) domains in modulating transcription factor activity

Kathrin Schrick12*, Michael Bruno3, Aashima Khosla1, Paige N Cox1, Sara A Marlatt2, Remigio A Roque2, Henry C Nguyen2, Cuiwen He2, Michael P Snyder3, Daljit Singh4 and Gitanjali Yadav4

Author Affiliations

1 Division of Biology, Kansas State University, Manhattan 66506, KS, USA

2 Keck Graduate Institute of Applied Life Sciences, Claremont 91711, CA, USA

3 Department of Genetics, Stanford University, Stanford 94305, CA, USA

4 National Institute of Plant Genome Research, New Delhi, India

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BMC Biology 2014, 12:70  doi:10.1186/s12915-014-0070-8

Published: 27 August 2014



Steroidogenic acute regulatory protein (StAR)-related lipid transfer (START) domains were first identified from mammalian proteins that bind lipid/sterol ligands via a hydrophobic pocket. In plants, predicted START domains are predominantly found in homeodomain leucine zipper (HD-Zip) transcription factors that are master regulators of cell-type differentiation in development. Here we utilized studies of Arabidopsis in parallel with heterologous expression of START domains in yeast to investigate the hypothesis that START domains are versatile ligand-binding motifs that can modulate transcription factor activity.


Our results show that deletion of the START domain from Arabidopsis Glabra2 (GL2), a representative HD-Zip transcription factor involved in differentiation of the epidermis, results in a complete loss-of-function phenotype, although the protein is correctly localized to the nucleus. Despite low sequence similarly, the mammalian START domain from StAR can functionally replace the HD-Zip-derived START domain. Embedding the START domain within a synthetic transcription factor in yeast, we found that several mammalian START domains from StAR, MLN64 and PCTP stimulated transcription factor activity, as did START domains from two Arabidopsis HD-Zip transcription factors. Mutation of ligand-binding residues within StAR START reduced this activity, consistent with the yeast assay monitoring ligand-binding. The D182L missense mutation in StAR START was shown to affect GL2 transcription factor activity in maintenance of the leaf trichome cell fate. Analysis of in vivo protein┬┐metabolite interactions by mass spectrometry provided direct evidence for analogous lipid-binding activity in mammalian and plant START domains in the yeast system. Structural modeling predicted similar sized ligand-binding cavities of a subset of plant START domains in comparison to mammalian counterparts.


The START domain is required for transcription factor activity in HD-Zip proteins from plants, although it is not strictly necessary for the protein┬┐s nuclear localization. START domains from both mammals and plants are modular in that they can bind lipid ligands to regulate transcription factor function in a yeast system. The data provide evidence for an evolutionarily conserved mechanism by which lipid metabolites can orchestrate transcription. We propose a model in which the START domain is used by both plants and mammals to regulate transcription factor activity.

Transcription; Steroidogenic acute regulatory related lipid transfer; START; StAR; Homeodomain; HD-Zip; Glabra2; Yeast; Arabidopsis; Mouse